Oliver Nora T, Hartman Christine M, Kramer Jennifer R, Chiao Elizabeth Y
aDepartment of Medicine, Section of Infectious Diseases and Health Services Research, Baylor College of Medicine bCenter for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.
AIDS. 2016 Oct 23;30(16):2469-2476. doi: 10.1097/QAD.0000000000001219.
Chronic HIV/hepatitis C virus (HCV) coinfection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression.
Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999-2010). HIV-related variables included combination antiretroviral therapy era of diagnosis, CD4 cell count, and percentage time with undetectable HIV viral load. Metabolic variables included diabetes, low high-density lipoprotein (HDL), and hypertension. Statin use was measured as percentage time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (International Classification of Diseases-9 or aminotransferase-to-platelet ratio index >2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40 IU/l.
The cohort included 5985 HIV/HCV coinfected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT 40 IU/l or less; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (hazard ratio 0.68, 95% confidence interval 0.47-0.98). Diabetes and low HDL were significantly associated with cirrhosis in patients with ALT greater than 40 IU/l (hazard ratio 1.15, P < 0.04 and hazard ratio 1.3, P < 0.0001).
Statin drug use is beneficial in mitigating the risk of liver disease progression for HIV/HCV coinfected patients without advanced liver disease. Low HDL and diabetes in coinfected patients with abnormal ALT have greater risk of cirrhosis development.
慢性HIV/丙型肝炎病毒(HCV)合并感染会增加肝硬化、肝细胞癌和死亡的风险。由于具有抗炎特性,3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)抑制剂(他汀类药物)可能是减少肝脏疾病进展的有用辅助治疗方法。
从退伍军人事务部HIV和HCV临床病例登记处(1999 - 2010年)提取临床信息。与HIV相关的变量包括诊断时的联合抗逆转录病毒治疗时代、CD4细胞计数以及HIV病毒载量检测不到的时间百分比。代谢变量包括糖尿病、低高密度脂蛋白(HDL)和高血压。他汀类药物的使用以有活性处方的时间百分比来衡量(在整个随访期间随时间更新)。采用Cox比例风险分析来确定肝硬化的危险因素(国际疾病分类-9或转氨酶与血小板比值指数>2),总体以及在按丙氨酸转氨酶(ALT)水平高于和低于40 IU/l分层的组中。
该队列包括5985名HIV/HCV合并感染的退伍军人。大多数为黑人,索引日期时的平均年龄为45岁。对于ALT为40 IU/l或更低的患者,使用他汀类药物对肝硬化有显著的保护作用;他汀类药物使用时间每增加30%,发生肝硬化的风险降低32%(风险比0.68,95%置信区间0.47 - 0.98)。糖尿病和低HDL与ALT大于40 IU/l的患者发生肝硬化显著相关(风险比1.15,P<0.04;风险比1.3,P<0.0001)。
对于没有晚期肝病的HIV/HCV合并感染患者,使用他汀类药物有助于降低肝脏疾病进展的风险。ALT异常的合并感染患者中,低HDL和糖尿病发生肝硬化的风险更高。